The cell-to-cell
signaling role of
d
-amino acids (
d
-AAs) in the mammalian
endocrine system, particularly in the
islets of Langerhans, has drawn growing interest for their potential
involvement in modulating glucose metabolism. Previous studies found
colocalization of serine racemase [produces
d
-serine (
d
-Ser)] and
d
-alanine (
d
-Ala) within insulin-secreting
beta cells and
d
-aspartate (
d
-Asp) within glucagon-secreting
alpha cells. Expressed in the islets, functional
N
-methyl-
d
-aspartate receptors are involved in the modulation
of glucose-stimulated insulin secretion and have binding sites for
several
d
-AAs. However, knowledge of the regulation of
d
-AA levels in the islets during glucose stimulation as well
as the response of islets to different levels of extracellular
d
-AAs is limited. In this study, we determined the intracellular
and extracellular levels of
d
-Ser,
d
-Ala, and
d
-Asp in cultures of isolated rodent islets exposed to different
levels of extracellular glucose. We found that the intracellular levels
of the enantiomers demonstrated large variability and, in general,
were not affected by extracellular glucose levels. However, significantly
lower levels of extracellular
d
-Ser and
d
-Ala were
observed in the islet media supplemented with 20 mM concentration
of glucose compared to the control condition utilizing 3 mM glucose.
Glucose-induced oscillations of intracellular free calcium concentration
([Ca
2+
]
i
), a proxy for insulin secretion, were
modulated by the exogenous application of
d
-Ser and
d
-Ala but not by their
l
-stereoisomers. Our results provide
new insights into the roles of
d
-AAs in the biochemistry
and function of pancreatic islets.